One of the most heralded developments in basic science to reach clinical application in recent years has been the polymerase chain reaction (PCR). This technique of DNA amplification, which has already had an enormous effect on the way in which molecular biology research is done (and whose inventor, Kary Mullis, was awarded the Nobel Prize in Chemistry in 1993 in recognition of the extraordinary impact of PCR technology on scientific research generally), was quickly appreciated by clinical investigators as having potentially widespread utility in the early diagnosis of a wide range of disorders, such as inherited illnesses and infectious diseases (1). This Commentary will review the application of PCR to the diagnosis and evaluation of respiratory infections. The underlying principle guiding this Commentary is that the ideal diagnostic test for respiratory infectious disease should have the following characteristics: high sensitivity and specificity, high positive and negative predictive value, rapid turnaround time, ease of performance, reliability across samples (the same sample tested repeatedly should give the same result) and across those performing the assay (different laboratories performing the assay on the same specimen will report the same result), and low cost. It is against these criteria that PCR will be measured in this review.